This proposal seeks funds to purchase a Finnigan ProteomeX quadrupole ion trap mass spectrometry (MS) system for high-throughput protein analysis of complex biological samples. The requested instrumentation is essential for the emerging research needs of eight NIH sponsored major users at the Weill Medical College of Cornell University. The system will be made available to its users by inclusion in the Medical College's Mass Spectrometry CORE, a facility that has committed institutional support, 2 FTEs and which has been operational since 1997. The MS CORE facility provides the sole source of macromolecule mass spectrometric analysis to researchers at the Weill Medical College and associated hospitals. It is increasingly apparent, in this post-genomic era that the standard approach of defining patterns of gene expression provides an inadequate understanding of biological systems and processes. Proteomics is the study of the set of proteins within a cell, tissue, or organism. MS-based methods have enabled fledgling attempts at proteome elucidation. The conventional approach towards studying complex protein mixtures has involved two-dimensional electrophoresis of samples, followed by excision of interesting spots, and then MALDI-based peptide fingerprinting. Recently, a variety of powerful, new and high-throughput technologies have been developed which rely on MS, but substitute two-dimensional liquid chromatography for gel electrophoresis. Such new approaches have been successfully employed in numerous studies to rigorously identify thousands of proteins in a biological sample and to specify posttranslational protein modifications and changes in protein expression level. Here we propose to make such instrumentation for proteomic analyses available to biomedical scientists at the Weill Medical College. Access to these technologies is anticipated to greatly expand the scope and quality of science performed by a group of investigators whose research interests vary from fundamentals of cell signaling, to neuronal protein pattern analysis to identification of proteins involved in the pathogenesis of tuberculosis infections. Award of an integrated 2D chromatography ion trap MS system will extend the scope of services offered by the Weill Cornell MS CORE facility and strengthen the research of a diverse group of biomedical scientists. [unreadable] [unreadable]